Docetaxel-Loaded Electrospun Nanofibrous Mats for Local Chemotherapy Targeting Positive Surgical Margins in Prostate Cancer.

Abstract

Positive surgical margins following radical prostatectomy significantly contribute to tumor recurrence. While systemic chemotherapy demonstrates limited efficacy in this context, local chemotherapy drug delivery systems based on nanomaterials offer promising strategies to address this issue by modifying drug release kinetics and distribution, thereby enhancing antitumor effects while minimizing the toxicities associated with systemic chemotherapy. In this study, we utilized electrospun nanofibrous mats loaded with docetaxel for sustained drug delivery. In vitro experiments demonstrated that these implantable drug-loaded nanofibrous mats effectively inhibited prostate cancer cell growth, induced cell cycle arrest, and promoted apoptosis. In animal models, these drug-loaded nanofibrous mats exhibited prominent therapeutic effects on positive surgical margins postoperatively. Importantly, docetaxel-loaded nanofibrous mats modulated the tumor immune microenvironment by suppressing M2-like macrophages, increasing the ratio between M1- and M2-like macrophages, and enhancing CD8+ T-cell infiltration. Local administration significantly reduced systemic toxicity compared to systemic chemotherapy. In summary, we developed an implantable electrospun drug-loaded nanofibrous mat for localized docetaxel delivery, which offers a prospective strategy for managing positive surgical margins after surgery.